Ultrasound assisted synthesis of δ-chloroesters from tetrahydrofuran and acyl chlorides in the presence of catalytic zinc dust

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<ul><li><p>eschzi</p><p>, Y</p><p>e Cam</p><p>Yada</p><p>form</p><p>line 7</p><p>) in t</p><p> 2005 Elsevier B.V. All rights reserved.</p><p>known. Chemical ultrasonics began in 1927 when the</p><p>On the other hand, metal-assisted reactions are very</p><p>popular in organic syntheses due to their catalytic nat-</p><p>ported the preparation of 1,2-diketones from acid</p><p>Simple ethers such as dialkyl, aryl alkyl, diaryl, aryl</p><p>allyl and dibenzoyl ethers have been shown earlier to</p><p>give a mixture of the ester and the respective halide in</p><p>moderate to good yields in presence of transition metal</p><p>salts such as Mo, W, Pd and Co [2226]. These methods,</p><p>.</p><p>* Corresponding author. Tel.: +91 80 22245566.</p><p>E-mail address: m_af_pasha@yahoo.co.in (M.A. Pasha).</p><p>Ultrasonics Sonochemistry 131350-4177/$ - see front matter 2005 Elsevier B.V. All rights reservedacceleration of a conventional reaction was reported</p><p>by Richards and Loomis [1]. Since then, a number ofchemical reactions have been observed in an ultrasound</p><p>eld [27]. Sonic condition not only accelerates chemical</p><p>reactions, it reduces the number of steps which are re-</p><p>quired using normal conditions, cruder reagents can be</p><p>used and reactions can be initiated without any addi-</p><p>tives. The chemical eects of ultrasound are due to the</p><p>phenomenon of acoustic cavitation [8]. The primary</p><p>chemical reactions result from a transient state of hightemperatures and pressures [9]. Under sonic conditions,</p><p>the yields are high and the reactions occur in shorter</p><p>reaction durations.</p><p>chlorides and lithium under sonic conditions [10].</p><p>In continuation of our work on the use of inexpen-sive, readily available metals and metal salts for organic</p><p>functional group transformations [1121], we expected</p><p>that acid chlorides may be converted to 1,2-diketones</p><p>by zinc metal in aprotic solvents. A set of four sol-</p><p>ventshexane, toluene, benzene and THF were selected</p><p>to study the reaction of acyl halides with zinc dust under</p><p>sonic conditions. While studying these reactions in dry</p><p>THF, we found that acid chlorides react readily withTHF in the presence of catalytic amounts of zinc metal</p><p>to give d-chloroesters by the opening of the etherlinkage.Keywords: d-chloroesters; Tetrahydrofuran (THF); Acyl chlorides; Zinc dust; Ultrasound</p><p>1. Introduction</p><p>The application of power ultrasound to chemical syn-</p><p>theses and its use in research and in industries are well</p><p>ure, selectivity and simple work-up. A number of reac-</p><p>tions with metals under dierent reaction conditions</p><p>for the reduction of dierent functional groups are doc-</p><p>umented in the literature. Boudjouk and Han have re-Ultrasound assisted synthtetrahydrofuran and acyl</p><p>catalytic</p><p>M.A. Pasha a,*</p><p>a Department of Studies in Chemistry, Central Collegb Department of Chemistry,</p><p>Received 26 October 2004; received in revised</p><p>Available on</p><p>Abstract</p><p>Sonication of acyl chlorides and dry tetrahydrofuran (THF</p><p>d-chloroesters in high yields.doi:10.1016/j.ultsonch.2005.01.003is of d-chloroesters fromlorides in the presence ofnc dust</p><p>i Yi Myint a,b</p><p>pus, Bangalore University, Bangalore 560 001, India</p><p>nabon University, Myanmar</p><p>11 January 2005; accepted 14 January 2005</p><p>April 2005</p><p>he presence of catalytic amounts of zinc dust at 35 kHz gives</p><p>www.elsevier.com/locate/ultsonch</p><p>(2006) 175179</p></li><li><p>however, take a long time for completion of the reac-</p><p>tion, take place at high temperatures, and give a mixture</p><p>of products.</p><p>On the other hand, THF has been found to react with</p><p>acyl chlorides in the presence of 25 mole% Zn metal in</p><p>diethyl ether as solvent to give d-chloroesters. This reac-tion takes 318 h for completion [27]. As the reactions</p><p>are studied in Et2O there exists an ambiguity in the reac-tion with the possibility of Et2O reacting with acyl chlo-</p><p>rides in the presence of Zn metal to give the respective</p><p>alkyl chloride and the ester in the reaction mixture,</p><p>along with the corresponding d-chloroester.</p><p>well as under the inuence of ultrasound in a sonic bath</p><p>operating at 35 kHz to give d-chloroesters in high yields</p><p>from THF and benzoyl chloride; the results are summa-</p><p>rized in Table 1. From the table, it is clear that the reac-</p><p>tion can be carried out in presence of catalytic amounts</p><p>of zinc dust (1 mmol) and that it is not possible without</p><p>zinc dust (entry 5).</p><p>Under normal (silent) condition, benzoyl chloride,THF (taken in excess which also serves as solvent) and</p><p>zinc dust (catalytic) were stirred at 25 C. The reactionwas monitored by TLC (5% EtOAc: pentane) and went</p><p>to completion in 2 h to give 4-chlorobutyl benzoate in</p><p>90% yield.</p><p>In order to extend the reaction of THF with dierent</p><p>acyl halides in the presence of catalyst zinc dust to get d-chloroesters, the study of reaction of THF with alkyl,aryl and allyl substituted acyl chlorides was taken up.</p><p>The reactions were carried out under silent conditions</p><p>as well as under the inuence of ultrasound. These</p><p>results are summarized in Table 2.</p><p>From Table 2 it is clear that the reaction takes about</p><p>124 h for completion under normal (silent) conditions.</p><p>s of z</p><p>O+</p><p>))))</p><p>Zn (cat)RCOO(CH2)3CH2ClRCOCl</p><p>R= CH 3, ClCH2, C6H5, p-ClC6H4,</p><p>p-BrC6H4, p-NO2C6H4, C6H5CH=CH</p><p>Scheme 1.</p><p>176 M.A. Pasha, Y.Y. Myint / Ultrasonics Sonochemistry 13 (2006) 175179as shown in Scheme 1.</p><p>2. Results and discussion</p><p>In order to standardize the reaction, dierentamounts of zinc dust were used to get d-chloroesters</p><p>Table 1</p><p>Reaction of THF and benzoyl chloride in presence of dierent amount</p><p>Entry Amount of Zn (mmol) Product</p><p>1 20</p><p>Cl</p><p>2 10We now wish to report the results of our study of the</p><p>reactions of dierent acyl chlorides with THF in pres-</p><p>ence of catalytic amounts of zinc dust in the absence</p><p>of any additional solvent under normal conditions asCl</p><p>3 5Cl</p><p>4 1Cl</p><p>5 Nil No reactionAs the reaction takes a long time for completion [except</p><p>the reaction with acetyl chloride (entry 1)], the reactionwas carried out in a sonic bath working at 35 kHz. A</p><p>noteworthy feature of this reaction is that the rate of</p><p>the reaction gets accelerates and the reaction goes to</p><p>completion within 550 min under the inuence of ultra-</p><p>sound and dierent d-chloroesters are obtained in highyields.</p><p>It is also clear that, THF ring can be readily opened</p><p>up by dierent acyl chlorides in the presence of catalyticamounts of zinc dust under sonic condition. While the</p><p>yields of the products vary between 76% and 86% and</p><p>the reaction takes up to 24 h for completion under silent</p><p>condition, yields of the respective products under the</p><p>inc dust under normal conditions</p><p>Time (h) Yield (%)</p><p>O</p><p>O</p><p>2 85</p><p>O</p><p>O</p><p>2 85</p><p>O</p><p>O</p><p>2 87</p><p>O</p><p>O</p><p>2 9024 </p></li><li><p>Normal condition Sonic condition</p><p>Time (h) Yield (%) Time (min) Yield (%)</p><p>0.1 86 5 94</p><p>1 85 15 93</p><p>2 90 30 94</p><p>O</p><p>12 80 50 96</p><p>O2</p><p>3 78 30 92</p><p>l</p><p>nics Sonochemistry 13 (2006) 175179 1775O2N Cl OCl</p><p>O</p><p>6Cl</p><p>O</p><p>Cl ClO</p><p>CTable 2</p><p>Reaction of acyl chlorides with THF in presence of zinc dusta</p><p>Entry Acid chloride Product</p><p>1 O</p><p>Cl</p><p>O</p><p>OCl</p><p>2 ClO</p><p>Cl</p><p>O</p><p>OCl Cl</p><p>3</p><p>Cl</p><p>O</p><p>ClO</p><p>O</p><p>4</p><p>O</p><p>Br Cl</p><p>Br</p><p>ClO</p><p>NO</p><p>M.A. Pasha, Y.Y. Myint / Ultrasoinuence of ultrasound are between 92% and 96%. The</p><p>reaction is general, as dierent acyl chlorides including</p><p>aroyl chlorides having electron-releasing or electron-</p><p>withdrawing groups react satisfactorily to give d-chloro-esters within 50 min.</p><p>3. Mechanism</p><p>The reaction of acyl chlorides with THF in the pres-</p><p>ence of catalytic amounts of zinc dust under the inu-</p><p>ence of ultrasound is expected to proceed as shown in</p><p>Scheme 2. In the rst step of the reaction, catalytic</p><p>amounts of ZnCl2 is expected to form by the reaction</p><p>between zinc and acyl chloride. This ZnCl2 may react</p><p>with another molecule of acyl chloride to give acyl cat-ion and ZnCl3 in the step II. In step III, acyl cationso formed may react with THF to give an oxonium</p><p>ion intermediate and in the step IV, ZnCl3 may interactwith this oxonium ion intermediate to give the ring</p><p>opening product d-chloroester.In fact, we have found that, catalytic amount of</p><p>ZnCl2 is sucient to initiate the reaction under sonic</p><p>condition, and this catalytic cycle continues till the com-pletion of the reaction. As the reaction involves the for-</p><p>O7</p><p>O</p><p>Cl ClO</p><p>Oa Products are identied by the IR and 1H NMR spectral analysis.1 86 15 95mation of a primary carbocation in the IV step of the</p><p>reaction to regenerate ZnCl2, the reaction is expected</p><p>to proceed by SN2 mechanism to give the product.</p><p>Zn (Cat) CH3COCl</p><p>ZnCl2</p><p>CH3COCl</p><p>CH3CO+ ZnCl3</p><p>_</p><p>_</p><p>COCH3</p><p>O</p><p>O</p><p>ZnCl3</p><p>Cl</p><p>OCOCH3</p><p>) )))</p><p>+</p><p>+</p><p>+</p><p>SN2</p><p>I</p><p>II</p><p>IIIIV</p><p>Scheme 2.</p><p>24 84 50 95</p></li><li><p>Dierent acyl chlorides were prepared by standard</p><p>procedures [28] and puried before use. All reagents</p><p>Table3</p><p>Spectraldata</p><p>(IRand</p><p>1H</p><p>NMR)ofd-chloroesters</p><p>Entry</p><p>Product</p><p>IR[t(cm1)]</p><p>1H</p><p>NMR(CDCl 3)[d(ppm)]</p><p>1CH3CO2(CH2) 4Cl</p><p>1745,762</p><p>1.661.80[m,4H</p><p>(CH2CH2)],1.97[s,3H</p><p>(CH3CO)],3.49[t,2H</p><p>(CH2Cl),J=6Hz],4.01[t,2H</p><p>(CH2O),J=6Hz]</p><p>2ClCH2CO2(CH2) 4Cl</p><p>1750,762</p><p>1.61.9[m,4H</p><p>(CH2CH2)],2.05[s,2H{CH2(Cl)COO}],3.5[t,2H{CH2(Cl)CH2},J=6Hz],4.05[s,2H</p><p>(CH2O)]</p><p>3C6H5CO2(CH2) 4Cl</p><p>1729,721</p><p>1.93[m,4H</p><p>(CH2CH2)],3.59[qua,2H</p><p>(CH2Cl),J=4.1Hz],4.35[t,2H</p><p>(CH2O),J=4.1Hz],7.417.448.028.04</p><p>[m,5H</p><p>(C6H5)]</p><p>4BrC</p><p>6H4CO2(CH2) 4Cl</p><p>1734,765</p><p>1.9[m,4H</p><p>(CH2CH2)],3.55[m,2H</p><p>(CH2Cl)],4.35[m,2H</p><p>(CH2O)],7.557.67.857.91[dd,4H</p><p>(C6H4),J=8.2Hz]</p><p>5NO2C6H4CO2(CH2) 4Cl</p><p>1741,727</p><p>1.89[m,4H</p><p>(CH2CH2)],3.59[m,2H</p><p>(CH2Cl)],4.34[m,2H</p><p>(CH2O)],8.148.16,8.228.25[dd,4H</p><p>(C6H4),J=8Hz]</p><p>6ClC</p><p>6H4CO2(CH2) 4Cl</p><p>1709,746</p><p>1.95[m,4H</p><p>(CH2CH2)],3.60[m,2H(CH2Cl)],4.36[m,2H</p><p>(CH2O)],7.577.6,7.887.92[dd,4H</p><p>(C6H4),J=10Hz]</p><p>7C6H5CH@CHCO2(CH2) 4Cl</p><p>1770,768</p><p>1.9[m,4H</p><p>(CH2CH2)],3.61[m,2H(CH2Cl)],4.36[m,2H</p><p>(CH2O)],6.45[d,1H</p><p>{CH(OCO)@</p><p>CH},J=4Hz],7.48</p><p>[d,1H</p><p>{CH(C</p><p>6H5)@</p><p>CH},J=4Hz],7.8[m,5H</p><p>(C6H5)]</p><p>178 M.A. Pasha, Y.Y. Myint / Ultrasonics Swere obtained from Rankem. All the reactions were</p><p>studied using Julabo, USR-3 German made sonic bath</p><p>working at 35 kHz (constant frequency) maintained at</p><p>25 C by constant circulation of water, without mechan-ical stirring. A Nicolet 400D FT-IR spectrophotometer</p><p>was used for IR spectral analysis. NMR spectra were re-</p><p>corded on a 400 MHz Bruker instrument. The chemical</p><p>shift values (d ppm) reported are relative to TMS inCDCl3 as solvent. Yields refer to the isolated yields of</p><p>the products and are based on 10 mmol of starting acyl</p><p>chloride.</p><p>4.2. General experimental procedure for the preparation</p><p>of CH3COO(CH2)4Cl</p><p>4.2.1. Under sonic condition</p><p>Benzoyl chloride (1.41 g, 10 mmol), THF(10 mL) and</p><p>zinc dust (0.065 g, 1 mmol) were sonicated in a bath at</p><p>35 kHz, while maintaining the temperature of the bath</p><p>at 25 C. The reaction went to completion in 30 min(TLC 5% EtOAc: pentane), the contents were extracted</p><p>with ether (3 10 mL), and the combined ethereal ex-tract was washed with saturated NaHCO3 solution,</p><p>water, and then dried over anhydrous Na2SO4. The sol-vent was then removed under vacuum and the crude was</p><p>subjected to silica gel chromatography using 5% EtOAc:</p><p>pentane to get 4-chlorobutyl benzoate (2.00 g, 94%</p><p>yield).</p><p>4.2.2. Under normal condition</p><p>A mixture of benzoyl chloride (1.41 g, 10 mmol),</p><p>THF (10 mL) and zinc dust (0.065 g, 1 mmol) was stir-red at 25 C. The reaction was monitored by TLC (5%EtOAc: pentane) and was complete in 2 h. After comple-</p><p>tion of the reaction, the contents were taken into ether</p><p>(30 mL), and the ethereal solution was washed with sat-</p><p>urated NaHCO3 solution and water, and then dried over</p><p>anhydrous Na2SO4. The solvent was removed under</p><p>vacuum and the crude was subjected to silica gel chro-</p><p>matography using 5% EtOAc: pentane to get 4-chlo-robutyl benzoate (1.91 g, 90%). The IR and 1H NMR</p><p>spectral data of the d-chloroesters prepared by this pro-cedure are presented in Table 3.</p><p>5. Conclusion</p><p>In conclusion, we have developed a simple and eco-nomically viable method for the preparation of d-chlo-4. Experimental</p><p>4.1. Material and instruments</p><p>onochemistry 13 (2006) 175179roesters using catalytic amounts of inexpensive, readily</p></li><li><p>available, abundant zinc metal, THF and acyl chlorides</p><p>under sonic condition. These d-chloroesters are impor-tant in organic syntheses and nd application in the syn-</p><p>theses of natural products where a four-carbon chain is</p><p>required to be added. From the point of view of work-</p><p>up and time for completion, the present reaction is supe-rior as compared to existing methods.</p><p>Acknowledgments</p><p>Yi Yi Myint acknowledges the Ministry of Educa-</p><p>tion, Government of Myanmar, the Bangalore Univer-</p><p>sity and Indian Council for Cultural Relations for afellowship and nancial assistance.</p><p>References</p><p>[1] W.T. Richards, A.L. Loomis, J. Am. Chem. Soc. 49 (1927) 3068.</p><p>[2] K.S. Suslick, Science 249 (1990) 1439.</p><p>[3] T.J. Mason, J.P. Lorimer, Sonochemistry: Theory, Applications</p><p>and Uses of Ultrasound in Chemistry, John Wiley and Sons, New</p><p>York, 1988.</p><p>[4] A. Wiessler, H.W. Coofer, S. Snyder, J. Am. Chem. Soc. 72</p><p>(1950) 1976.</p><p>[5] J.L. Luche, Synthetic Organic Sonochemistry, Plenum, New</p><p>York, 1998.</p><p>[6] J.P. Lorimer, T.J. Mason, Chem. Soc. Rev. 16 (1987) 239.</p><p>[7] K.S. Suslick, Modern Synthetic Methods 4 (1986) 1.</p><p>[8] T.J. 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(S) 5 (2004) 333.</p><p>[21] Y.Y. Myint, M.A. Pasha, Synth. Commun. 34 (2004) 2829.</p><p>[22] J.K. Stille, I.P. Bar, J. Org. Chem. 47 (1982) 1215.</p><p>[23] B. Ganem, V.R. Small, J. Org. Chem. 39 (1974) 3728.</p><p>[24] H. Alper, C.C. Haung, J. Org. Chem. 38 (1973) 64.</p><p>[25] M.H. Karger, Y. Mazur, J. Am. Chem. Soc. 90 (1968) 3878.</p><p>[26] J. Iqbal, S. Ahmad, Chem. Lett. (1987) 953.</p><p>[27] S. Bhar, B.C. Ranu, J. Org. Chem. 60 (1995) 745.</p><p>[28] A.I. Vogel, A Text Book of Practical Organic Chemistry, third</p><p>ed., ELBS, London, 1975, p. 367 and 791.</p><p>M.A. Pasha, Y.Y. Myint / Ultrasonics Sonochemistry 13 (2006) 175179 179</p><p>Ultrasound assisted synthesis of delta -chloroesters from tetrahydrofuran and acyl chlorides in the presence of catalytic zinc dustIntroductionResults and discussionMechanismExperimentalMaterial and instrumentsGeneral experimental procedure for the preparation of CH3COO(CH2)4ClUnder sonic conditionUnder normal condition</p><p>ConclusionAcknowledgmentsReferences</p></li></ul>